Variant rs4574 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002799.4(PSMB7):c.116T>C(p.Val39Ala) variant causes a missense change. The variant allele was found at a frequency of 0.431 in 1,612,794 control chromosomes in the GnomAD database, including 153,477 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.46 ( 16512 hom., cov: 31)

Exomes 𝑓: 0.43 ( 136965 hom. )

Consequence

PSMB7
NM_002799.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.36

Variant links:

Genes affected

PSMB7 (HGNC:9544): (proteasome 20S subunit beta 7) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. The encoded protein is a member of the proteasome B-type family, also known as the T1B family, and is a 20S core beta subunit in the proteasome. Expression of this catalytic subunit is downregulated by gamma interferon, and proteolytic processing is required to generate a mature subunit. A pseudogene of this gene is located on the long arm of chromosome 14. [provided by RefSeq, Jul 2012]

PSMB7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.8055054E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMB7	NM_002799.4 link	c.116T>C	p.Val39Ala	missense_variant	2/8	ENST00000259457.8	NP_002790.1	Q99436-1E9KL30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PSMB7	ENST00000259457.8 link	c.116T>C	p.Val39Ala	missense_variant	2/8	1	NM_002799.4	ENSP00000259457.3	Q99436-1
PSMB7	ENST00000441097.1 link	c.116T>C	p.Val39Ala	missense_variant	2/7	5		ENSP00000393157.1	Q5TBG5
PSMB7	ENST00000466951.1 link	n.231T>C		non_coding_transcript_exon_variant	2/4	3
PSMB7	ENST00000498485.5 link	n.233T>C		non_coding_transcript_exon_variant	2/7	5

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69191

AN:

151760

Hom.:

16500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.595

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.419

GnomAD3 exomes

AF:

0.401

AC:

100471

AN:

250412

Hom.:

21093

AF XY:

0.402

AC XY:

54365

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.604

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.239

Gnomad SAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.407

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.429

AC:

626386

AN:

1460916

Hom.:

136965

Cov.:

AF XY:

0.427

AC XY:

310667

AN XY:

726730

show subpopulations

Gnomad4 AFR exome

AF:

0.602

Gnomad4 AMR exome

AF:

0.325

Gnomad4 ASJ exome

AF:

0.350

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.407

Gnomad4 NFE exome

AF:

0.438

Gnomad4 OTH exome

AF:

0.421

GnomAD4 genome

AF:

0.456

AC:

69248

AN:

151878

Hom.:

16512

Cov.:

AF XY:

0.449

AC XY:

33361

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.595

Gnomad4 AMR

AF:

0.346

Gnomad4 ASJ

AF:

0.335

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.412

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.429

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.426

Hom.:

34480

Bravo

AF:

0.462

TwinsUK

AF:

0.443

AC:

1642

ALSPAC

AF:

0.431

AC:

1661

ESP6500AA

AF:

0.607

AC:

2673

ESP6500EA

AF:

0.435

AC:

3739

ExAC

AF:

0.408

AC:

49510

Asia WGS

AF:

0.323

AC:

1127

AN:

3478

EpiCase

AF:

0.420

EpiControl

AF:

0.413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.000098

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.7

N;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

2.4

N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;.

Vest4

0.029

MPC

0.42

ClinPred

0.015

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over